The efficacy and safety of fixed-dose abacavir/lamivudine against tenofovir/emtricitabine, both with once-daily darunavir/ritonavir, was examined in 80 treatment-naïve patients with a baseline HIV-1 viral load of more than 100 000 copies/ml. The time to virologic failure by 48 weeks was not different between the two groups. The percentage of patients with viral suppression was not significantly different with per protocol population. Tenofovir/emtricitabine showed better tolerability; more patients on abacavir/lamivudine changed regimen than those on tenofovir/emtricitabine. A randomized trial to elucidate the efficacy and safety of these two regimens is warranted.